We plan to a) incubate in vitro propagated epithelioid rat liver cells with chemical carcinogens such as methylazoxymethanol acetate, dimethylnitrosamine and other nitrosamines and b) inject carcinogens into partially hepatectomized rats and remove liver tissue for culture at various times thereafter. The cells will be examined for early changes in morphology, surface membrane reactivity and the appearance of antigenic modification. Attempts will be made to refine and devise new tests for the recognition of preneoplastic alterations. Such systematic studies of the transformation of differentiated epithelioid cells are more pertinent to the cancer problem as it relates to carcinoma, the type of tumor most frequently found in man, and might provide clues for the detection of early stages of oncogenesis.